Biophysical implants are becoming more common in medicine. Those implants that couple directly to a recipient's nervous system provide a way to control or influence various neurological functions, as well as offer a way to measure biological responses to the implants. Such devices include brain implants, retinal implants and cochlear implants.
Electrophysiology involves measurements of electrical changes and properties of biological cells and tissues, including neurons where the electrical activity is the action potential. A compound action potential (CAP) is the summed responses of a number of neurons firing together.
A widely used and advanced form of biophysical implant is the auditory prosthesis, in particular the cochlear implant (also commonly referred to as cochlear prostheses, cochlear devices, or cochlear implant devices).
Hearing loss, which can have a number of different causes, is generally of two types, conductive (when the normal mechanical pathways of the outer and/or middle ear are impeded), and/or sensorineural (when there is damage to the inner ear, or to the nerve pathways from the inner ear to the brain).
Those suffering from some forms of sensorineural hearing loss benefit from implantable auditory prostheses that electrically stimulate nerve cells of the recipient's auditory system. Cochlear implants are typically prescribed when the sensorineural hearing loss is due to the absence or destruction of the cochlea hair cells, whose prime role is to transduce acoustic signals into nerve impulses.
Cochlear implants generally include a stimulating assembly implanted in a recipient's cochlea to deliver electrical stimulation signals to the auditory nerve cells, thereby bypassing absent or defective hair cells in the cochlea. The electrodes of the stimulating assembly differentially activate auditory neurons that normally encode differential pitches of sound. This assembly enables the brain to perceive a hearing sensation resembling the natural hearing sensation normally delivered to the auditory nerve from the hair cells. An exemplary cochlear implant system is sold by Cochlear Limited (Sydney, Australia) under the Nucleus® brand.
Cochlear implants have historically comprised a receiver/stimulator unit implanted in the recipient's mastoid bone, and an external speech processor unit worn on the body of the recipient which wirelessly transmits information to the implant via RF signals or some other suitable wireless data and/or audio transmission scheme. More recent trends include combining the external and implanted units to produce a “totally implantable cochlear implant” (TICI) capable of operating, at least for a period of time, without the need for an external device.
In any case, the speech processor detects external sound and converts that sound into a coded signal via a suitable speech processing algorithm. From an external unit, the coded signal is sent to the implanted receiver/stimulator unit via a transcutaneous link. For a totally implanted system, detected sound is directly processed by a speech processor within the stimulator unit, with the subsequent stimulation signals delivered without the need for any transcutaneous transmission of signals. Regardless of where the external sound is detected, the receiver/stimulator unit processes the coded signal to generate a series of stimulation sequences which are then applied directly to the auditory nerve via an array of electrodes positioned within and proximal to the modiolus of the recipient's cochlea.
The effectiveness of auditory prostheses depends not only on their specific design but also on how well a prosthesis is configured for, or “fitted” to, the recipient. The fitting, sometimes referred to as “programming” or “mapping” of the prosthesis, creates configuration settings and other data (commonly referred to as a MAP) that define the specific characteristics of the signals (acoustic, mechanical, or electrical) delivered to the recipient. This requires obtaining data about the actual performance of the electrode array following implantation, as well as the response of the auditory nerve to stimulation. Such data collection enables detection and confirmation of the normal operation of the device, and allows the stimulation parameters to be optimized (fitted) to suit the needs of the recipient.
Typically, fitting is manually performed by applying stimulation pulses for each channel and receiving an indication from the implant recipient as to the level and comfort of the resulting sound that the recipient perceives. (As used herein, a channel is the collection of two or more electrodes between which current may be caused to flow to create an auditory percept.) For implants with a large number of channels for stimulation, this process is quite time consuming and rather subjective as it relies heavily on the recipient's subjective impression of the stimulation rather than an objective factor such as a specific measurement. This aspect is further complicated in the case of children and pre-lingual or congenitally deaf patients who are unable to supply an accurate impression of the resulting hearing sensation when asked. In such cases, an incorrectly fitted implant may result in the recipient not receiving optimum benefit from it, and in the case of children, may directly hamper their speech and hearing development. Therefore, there is a need to obtain accurate objective measurements of patient specific data especially in cases where reliable subjective feedback is not possible.
One method of interrogating the performance of the implanted device is to directly measure electrically evoked compound action potentials (EECAPs). The term “evoked” is used herein in a manner synonymous with stimulation: a new response (super-imposed on the basal response of the nerve) is created as a result of an input stimulus. Following electrical stimulation, the neural response is caused by the superposition of single neural responses at the outside of the axon membranes. The EECAP can then be measured as the collective response of all neurons within a nerve or nerve portion to various stimulations, and from this the performance of the implant can be assessed and patient parameters can be interpolated. Neural response telemetry (NRT) is another term used in the art for measures of the responses of nerve cells to an evoked electrical potential. Thus, recording an EECAP with a cochlear implant provides an objective measurement of the response of the auditory nerve to an electrical stimulus (as delivered by an implant electrode).
Additionally, the measurement of ECAPs has provided a useful objective quantification of many applications, such as cortical recordings, auditory brain stem recordings, and electrocochleography (“ECOG”). The last of these, ECOG, measures auditory nerve responses that are evoked acoustically rather than electrically, which means that the measured response includes contributions from the motions of the hairs in the inner ear, the distension of the basal membrane, as well as other physiological effects.
A number of methods and devices to measure evoked compound action potentials (ECAPs) have been developed for cochlear implants. Such systems have used the electrodes implanted within the cochlea to both deliver electrical stimulation and to detect the responses of the nerves to such stimulation.
An aural ECAP comprises contributions from several points along the auditory pathway between the outer ear and the inner brain. The contributions are generally referred to via the wave number. Waves I and II are understood to arise primarily from the cochlea nucleus; waves III-V are typically thought to arise from the brain stem responses; and waves VI and VII are typically thought to correspond to mid brain responses. Cortical responses arise from higher level processes and have much higher latencies still.
Nevertheless, systems for measuring ECAPs still have a number of intrinsic limitations, which have affected the quality of measurements of the neural responses made with them. In the main, this has been due to the presence of artifacts in the measured responses, which mean that the measurement is not necessarily a true indication of the actual ECAP response.
The process of distinguishing the actual ECAP from artifacts has presented considerable difficulties, such as the fact that the signals to be measured are extremely small (down to around 10 μV) in comparison to the size of the stimulus itself, which is typically many orders of magnitude greater (having an amplitude in the range of 1 V to 10 V).
Providing a system that is able to both deliver a stimulus of sufficient amplitude and to detect the elicited response of the nerves to that stimulus has therefore been challenging. Furthermore, due to the nature of the neural response, the detection system must be ready to record the response within a short delay (preferably less than 50 μs) after completion of the stimulus. In order to properly resolve the very small neural response signal from that of the stimulus, a large amplifier gain is required (typically of about 60 dB to 70 dB). But since the neural signal of interest is often superimposed on a much larger artifact, it is difficult to extract the neural signal due to the finite dynamic range of the amplifier and the need for high gain to resolve the signal.
In the past, many systems have simply ignored the artifacts due to acquisition and stimulation, and were not overly concerned about noise in the signal. Others have deployed advanced preparation and shielding techniques, but these are time consuming and laborious to apply, particularly in a surgical setting. Another way in which useful measurements have been separated from the associated artifacts has been through the use of extensive post processing techniques, such as filtering (e.g., by mathematical methods such as principal/independent component analysis (PCA, ICA)). These techniques have applied complicated algorithms to the raw measurements in an attempt to cancel out the presence of the artifacts. Such processes do not provide immediate results which can be acted upon during the fitting process, since the measured results often require time consuming analysis before they can be used. In other approaches, electrophysiological measurements require several baseline measurements, made without stimulation, in order to separately record the artifacts introduced by the acquisition system alone. This baseline measurement—where there is no stimulus artifact—is ultimately subtracted from subsequent averaged measurements of a stimulated response in an attempt to remove the acquisition artifacts. Averaging the measurements ensures the recording is not contaminated with neural responses, such as from spontaneous firing in the periphery (other brain activity in cortical and brain stem measurements). Even the act of inserting an electrode array into the cochlear (while simultaneously taking measurements) can lead to pressure of the electrode array against internal structures, which may evoke neural firing.
The need to take a baseline measurement slows the overall electrophysiological acquisition process, and it has been found to introduce additional noise into the measured results. Baseline subtraction methods and filtering are implemented at the signal processing stage, and do not therefore require adjustments to the electronic circuitry but are part of the programming of the system that captures the signal.
In still other approaches, the acquisition system components are modelled, and then the models are subtracted from the measured signals. But such methods depend on establishing reliable models and some level of calibration, neither of which is straightforward.
In yet other approaches, it is possible to differentiate a neural response from stimulus artifacts by one of two primary methods: forward masking, and alternating stimulation polarity. Forward masking has generally been the more effective of the two techniques. Forward masking involves defining two signals: a probe and mask. A probe is the stimulus that evokes a response. A mask is a secondary stimulus applied before the probe in time, which has the effect of putting the nerve into a refractory state so that it does not fire in response to the probe. This therefore “masks” the effect of the probe, thereby suppressing the response in the subject. The combination of the masker and probe stimulus results in a stimulation artifact which has no neural response present. If two measurements are made, one of the probe alone, and one of the probe-mask combination, the latter can be subtracted from the probe only measurement to remove the stimulation artifact (which is present in both measurements), and thereby isolate the neural response. Alternating stimulation polarity is achieved via dedicated switching circuitry in the stimulation system. Both of these techniques, masking and alternating stimulation, can be used in conjunction with the methods of reducing the acquisition-related artifact, as further described herein.
Overall, given the need to measure the response of nerves to electrical stimulation in many applications, not just in the area of cochlear implants, improvements in accuracy would be welcome. A reliable measurement of the ECAP in response to a given stimulation, would permit the effectiveness of the stimulation to be assessed in relation to the neural response that it evokes. There are various different points of potential measurement along the auditory signal chain. Other waveforms in the chain correspond to higher order functions of the brain, which can be measured in similar ways to ECAPs.
The discussion of the background herein is included to explain the context of the technology. This is not to be taken as an admission that any of the material referred to was published, known, or part of the common general knowledge as at the priority date of any of the claims found appended hereto.
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